dtsch_arztebl_int-108-0543

M E D I C I N E

REVIEW ARTICLE

Cluster HeadacheClinical Features and Therapeutic Options

Charly Gaul, Hans-Christoph Diener, Oliver M. Müller

SUMMARYBackground: Cluster headache is the most common type of trigemino-autonomic headache, affecting ca. 120 000 persons in Germany alone. The attacks of pain are in the periorbital area on one side, last 90 minutes on average, and are accompanied by trigemino-autonomic manifes-tations and restlessness. Most patients have episodic cluster headache; about 15% have chronic cluster head-ache, with greater impairment of their quality of life. The attacks often possess a circadian and seasonal rhythm.

Method: Selective literature review

Results: Oxygen inhalation and triptans are effective acute treatment for cluster attacks. First-line drugs for attack prophylaxis include verapamil and cortisone; alternatively, lithium and topiramate can be given. Short-term relief can be obtained by the subcutaneous infiltration of local anesthetics and steroids along the course of the greater occipital nerve, although most of the evidence in favor of this is not derived from randomized clinical trials. Patients whose pain is inadequately relieved by drug treatment can be offered newer, invasive treatments, such as deep brain stimulation in the hypothalamus (DBS) and bilateral occipital nerve stimulation (ONS).

Conclusion: Pharmacotherapy for the treatment of acute attacks and for attack prophylaxis is effective in most patients. For the minority who do not gain adequate relief, newer invasive techniques are available in some referral centers. Definitive conclusions as to their value cannot yet be drawn from the available data.

►Cite this as: Gaul C, Diener HC, Müller OM: Cluster headache—clini-cal features and therapeutic options. Dtsch Arztebl Int 2011; 108(33): 543–9. DOI: 10.3238/arztebl.2011.0543

C luster headache is the most common type of trigemino-autonomic headache (1), affecting

some 120 000 patients in Germany alone. This review article explains the clinical characteristics, diagnostic criteria, diagnostic approaches, differential diagnoses, and treatment options for cluster headache, so as to avoid delays to reaching the correct diagnosis and ini -tiating adequate treatment. The mean time period to diagnosis has been reported to be 44 months (e1). In ad-dition to the established medications for acute therapy and prophylaxis, newer options under discussion in-clude neuromodulation treatment for patients with chronic refractory cluster headache and are provided in specialist centers.

MethodsSelective review based on the authors’ scientific and clinical activities in the field.

Epidemiology The prevalence of cluster headache on the basis of population based samples is reported to be 7–119/100 000 (e2, e3). The epidemiological study of the German Migraine and Headache Society (Deutsche Migräne- und Kopfschmerzgesellschaft, DMKG) found a 12-month prevalence of 0.15%, the equivalent of about 120 000 people in Germany (2). This means that cluster headache is as common as multiple sclerosis (e4). More men are affected than women, with a ratio of 3.5:1 (3). The age of onset is around the 30th year of life, but cluster headache can also occur in children (4, e5). First-degree relatives have an 18-fold increased risk and second-degree relatives are at up to three times the risk of also developing the disease (e2).

Clinical featuresThe common characteristic of trigemino-autonomic headache disorders consists of brief, one-sided head-ache attacks and/or attacks of facial pain with ipsi -lateral autonomic symptoms. Typical comorbid symp-toms include lacrimation from the eye on the affected side, conjunctival reddening, rhinorrhea and/or nasal congestion, miosis and ptosis; in rare cases, contralat-eral sweating has been observed. More than 90% of those affected display pronounced restlessness during the attack, incessantly pacing the room or rocking the head and/or upper body (4). Ipsilateral Horner syndrome or permanent headache may persist between

Klinik und Poliklinik für Neurologie, Westdeutsches Kopfschmerzzentrum, Universitätsklinikum Essen: Dr. med. Gaul, Prof. Dr. med. Diener Klinik für Neurochirurgie, Universitätsklinikum Essen: Dr. med. Müller

Deutsches Ärzteblatt International | Dtsch Arztebl Int 2011; 108(33): 543–9 543

M E D I C I N E

attacks if these are very frequent and intense (e6). In 15% to 20% of patients, the headache changes sides during the course of their illness, but cluster headache never strikes bilaterally (4). In our patient collective, which we studied prospectively (n = 209), the average duration of an attack was 97 minutes. The attacks were primarily localized retro-orbitally or periorbitally and were described as stabbing and of the most severe in-tensity (“like a knife penetrating behind the eye”). Some patients experience pain in the face or even the teeth (orofacial cluster headache) (5). The severity of the pain and the frequency of the attacks seriously im-pair patients’ quality of life; 25% of patients reported suicidal intentions during the course of their illness (6). Aversion to light or sensitivity to noise are possible side effects, as are nausea and, rarer, visual aura (4). Particu-larly if symptoms are untypical, the diagnosis may be delayed, effective treatment not given, or even poten-tially harmful interventions administered; more than 20% of patients had surgery to their teeth or nasal sinuses (for example, if sinusitis was the suspected diagnosis) (e7).

The diagnostic criteria stipulate the occurrence of at least one attack every other day and up to eight attacks per day (Box 1, Table 1). Mostly, attacks follow a circa-dian pattern (mostly nocturnal attacks) or a seasonal rhythm (episodes mostly in spring and autumn). 85% of patients have episodic cluster headache, and some 15% chronic cluster headache, which develops secondary to episodic cluster headache or, more rarely, as primary chronic headache. Chronic cluster headache is defined as headache for at least one year, with attack-free inter-

vals of less than one month (1). In more than 80% of cases, cluster headache occurs episodically over many years (4). Cluster attacks are typically triggered by alcohol consumption. It is also of note that most of the patients with cluster headache are tobacco smokers (3). Whether smoking cessation has a favorable effect on the disease outcome is not known.

Pathogenesis of cluster headacheThe pathophysiology of cluster headache is not fully understood to date. Imaging procedures and hormone tests disproved the neurovascular theory of an inflam-matory process of the cavernous sinus and gave rise to the idea that high-level central dysregulation is the cru-cial pathomechanism of the disorder (7, 8, e8). The pos-terior hypothalamus has a key role in this, which might explain the circadian and seasonal pattern of the dis-order. While the hypothalamus as the supraordinate center is responsible for initiating attacks, the pain in the cranial autonomic nervous system is introduced and sustained by activation of parasympathetic and trigemi-nal nuclei (7, 8).

Diagnostic evaluation and differential diagnosis of cluster headache The diagnosis of cluster headache is made clinically according to the criteria set out in the International Classification of Headache Disorders (ICHD-II) (Box 1). An additional criterion is a normal clinical-neurological finding (1). Secondary manifestations of cluster headache as a result of inflammatory or neo-plastic processes in the cavernous sinus, the hypo -physeal fossa, or adjacent structures have to be ex-cluded by means of magnetic resonance imaging and, if required, computed tomography scanning of the skull-base. Especially adenomas of the pituitary gland need to be ruled out (e9, e10). As aneurysms close to the midline, arteriovenous malformations and dissections can also cause symptomatic cluster headache, MRI an-giography is useful to exclude vascular pathologies (e11). Signs of symptomatic cluster headache are an untypical time pattern, pathological findings on neur-ological examination, and a lack of, or unsatisfactory, response to otherwise effective therapies. In terms of differential diagnoses, cluster headache needs to be distinguished from paroxysmal hemicrania, which typi-cally responds to treatment with indomethacin. In pa-tients with accompanying pronounced autonomic symptoms, migraine should also be considered as a dif-ferential diagnosis. However, migraine attacks usually last longer than four hours and do not occur several times a day. Up to 30% of migraine patients do, however, report accompanying trigemino-autonomic symptoms—albeit less pronounced ones—mostly lacri-mation (9). In 25% of patients, cluster headache coincides with other headache types. Overlaps with migraine are known as cluster migraine; the simulta-neous occurrence of cluster headache with trigeminal neuralgia is known as cluster-tic syndrome (e12). Trigeminal neuralgia can also be accompanied by

BOX 1

Diagnostic criteria for cluster headache*A. At least 5 attacks fulfilling criteria B–DB. Severe or very severe unilateral orbital, supraorbital

and/or temporal pain lasting 15–180 minutes if un -treated.

C. Headache is accompanied by at least 1 of the following: – ipsilateral conjunctival injection and/or lacrimation – ipsilateral nasal congestion and/or rhinorrhea– ipsilateral eyelid edema– ipsilateral forehead and facial sweating – ipsilaterae miosis and/or ptosis– a sense of restlessness or agitation

D. Attacks have a frequency from 1 every other day to 8/day

E. Not attributed to another disorder.

* according to the International Classification of Headache Disorders (ICHD-II). Reproduced with permission of the International Headache Society

544 Deutsches Ärzteblatt International | Dtsch Arztebl Int 2011; 108(33): 543–9

M E D I C I N E

auto nomic symptoms, but, as a neuralgia, it is not classi -fied as a trigemino-autonomic headache. A distinction has to be drawn from nocturnal attacks of primarily sleep-related headache, which mostly develops after the 50th year of life (e13). Table 1 provides an over-view of the most important differential diagnoses.

Treating cluster headacheTherapeutically, the treatment of acute attacks needs to be distinguished from continuous treatment that aims to reduce the frequency and severity of the cluster attacks. Most therapies are empirically based; only few con-trolled studies exist, and the therapeutic recommen-dations of this article are based on our own experience, national and international therapeutic guidelines, small studies, and case series. Systematic reporting of effect sizes is therefore not possible (10–12) (Tables 2 and 3).

Acute treatment of cluster attacksInhaling oxygen (8–12 L/minute) through a close- fitting mouth-nose mask renders 78% of patients free of pain within 15 minutes (13). Oxygen can be prescribed in Germany as a medication that is covered by the statutory health insurers. Inhaling in a sitting position is said to be most effective; a rapid rebound and unsatis-factory effect in severe attacks are possible if oxygen inhalation is not begun immediately at the onset of the attack.

Triptans have shown a very beneficial and rapid effect; they can be administered subcutaneously (sum-atriptan 6 mg) or intranasally (zolmitriptan 5 mg or sumatriptan 20 mg). The number needed to treat (NNT) for pain reduction within 15 minutes is 2.4 for sub -cutaneously administered sumatriptan 6 mg and 2.8 for intranasal administration of 10 mg zolmitriptan (14). Pre-existing cardiac and cerebrovascular disorders, as

well as severe arterial hypertension are contraindi-cations for triptan use. If triptans are administered on a daily basis, a dull and pressing headache may develop that should be categorized as headache due to triptan overuse. This mostly affects patients with migraines or familial predisposition to migraines (e14).

To treat attacks, 4% to 10% lidocaine solution or 10% cocaine solution can be administered deep into the nostril, with the patient’s head reclining and rotated to the affected side. The effect is due to a local anesthetic block of the sphenopalatine ganglion (e15) by in-hibition of parasympathetic reflex pathways. The effec-tiveness is inferior to that of triptans, and many patients have reported a disagreeable burning sensation in their nose. Table 2 provides an overview of acute therapy.

Prophylaxis of cluster headacheProphylactic treatment of cluster headache is indicated in a setting of frequent and severe attacks; the aim is to shorten cluster episodes and reduce the number of at-tacks. Sufficient prophylaxis can help reduce triptan use and therapeutic expenditure. The prophylactic medications should be selected on the basis of thera-peutic experience, contraindications, and comorbid-ities; often, several prophylactic drugs are required. Table 3 provides an overview of prophylactic medications.

Verapamil is the drug of choice for the treatment of cluster headache. Because of its effects on cardiac con-duction, control ECGs are essential before and during therapy. The recommendations how rapidly the dose should be stepped up are inconsistent and are based on effectiveness and tolerability. The recommended maxi-mum daily dose is 560 mg. Higher dosages (up to 960 mg) should be given only once sufficient experience has been gained. Verapamil becomes effective within

TABLE 1

Differential diagnostic overview

*1 Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing *2 not classified as trigemino-autonomic headache disorder

*3 Lacrimation, ptosis, reddening, rhinorrhea or nasal congestion; ++, obligatory, pronounced; +, obligatory; (+), facultative

Duration of attacks

Frequency of attacks

Associatedautonomic symptoms*3

Particularities

Cluster headache

15–180 min

1–8/day

++

Oxygen is mostly effective

Paroxysmalhemicrania

2–30 min

5–15/day

++

Response to indomethacin required

SUNCTsyndrome*1

5–240 sec

3–200/day

+

Lamotrigine effective

Trigeminalneuralgia*2

1–120 sec

1 to hundreds/day

(+)

Carbamazepine mostly effective

Hemicraniacontinua*2

Continual pain, which exacer -bates in addition -al attacks

+

Response to indomethacin required

Headaches that primarily arise out of sleep*2

15–180 min

At least 15/month

(+) in 15% of patients

Arises exclusive-ly from sleep; age at initial manifestation mostly >50 years


M E D I C I N E

the first week of treatment and is superior to lithium in this respect (e16, e17). Lithium is an alternative to ver-apamil especially in the treatment of chronic cluster headache. Blood levels of lithium as well as of thyroid hormones should be measured regularly.

Corticoids are highly effective as the exclusive treat-ment in patients whose history has shown brief cluster episodes, or as temporary treatment until verapamil or lithium becomes effective, and for temporary treatment of a severe episode in chronic cluster headache (10). We have seen good results after administration of pred-nisone 100 mg over 5 days with subsequent gradual reduction (for example, reducing the dose by 20 mg on every third day). Depending on the experience gleaned from preceding cluster episodes, markedly higher do-sages may be required. In the short term, prednisone can be used at higher dosages and intravenously (10, e18). Because of their side effect profile, the long-term use of steroids is contraindicated.

Oral ergotamines have been found to be effective, but their variable gastrointestinal resorption, vasocon-strictive potential, and the potentially threatening side effects associated with ergotism constitute problems. Because of synergistic side effects, they should not be administered simultaneously with triptans. Ergota-mines can be taken in the evening as a prophylactic measure for nocturnal attacks (e14). The ergotamine alkaloid methysergide (8–12 mg) can be purchased from the international pharmacy. A combination with triptans, however, is problematic because of synergistic vasoconstrictive effects. Rare but potentially serious complications in long-term use are retroperitoneal, pleural, and cardiac valve fibrosis, so that laboratory controls, thoracic radiography, ECG, and abdominal ultrasonography should be undertaken after 4 to 6 months’ treatment. The treatment should be given for a

maximum of 6 months (e19). Because of the problem-atic side effects in long-term therapy, methysergide should be used only as third line pharmacotherapy and only by experienced practitioners.

Topiramate seems effective for cluster headache, but in our experience this is the case only for higher daily dosages (>100–150 mg/day) or in combination with verapamil and/or lithium. Adverse effects of topiramate include paresthesias and mental and cognitive impair-ments. Topiramate should not be used in patients with nephrolithiasis. Not enough study data are available, and topiramate is not licensed in Germany for use in cluster headache (e20). This is equally true for val-proate, gabapentin, melatonin, and pizotifen. Our own experiences with these substances have been disap-pointing (e21, e22), and they have hardly been included in routine clinical practice.

Nerve block anesthesia for the treatment of cluster headacheOccipital nerve block using a corticoid and a local an-esthetic may yield temporary relief. In a double blind, placebo controlled study, cluster attacks receded in some 85% of patients (15).

Cluster headache that is refractory to treatmentTo date, there is no uniform definition for treatment- refractory cluster headache (16, 17). It is therefore not possible to give an estimate of how many people are ac-tually affected. The DMKG guidelines define cluster headache as refractory if the disease takes a chronic course over 24 months with significant impairments to the patient’s quality of life and socioeconomic situ-ation. The guidelines recommend minimum dosages (verapamil >400 mg, lithium carbonate >800 mg and

TABLE 2

Therapeutic recommendations for the treatment of cluster attacks (modified from [12])

*1 Zolmitriptan 10 mg (2 × 5 mg) intranasally is superior to the 5 mg dose if the patient’s response is not satisfactory *2 Zolmitriptan 10 mg (2 × 5 mg) orally is possibly superior to the 5 mg dose if the patient’s response is not satisfactory ↑↑ Recommendation supported by several adequate, valid, clinical studies (e.g. randomized controlled trials [RCTs])

or by one or several valid meta-analyses or systematic reviews. Positive result well confirmed. ↑ Recommendation supported by at least one adequate, valid, clinical study (e.g. randomized controlled trial). Positive result confirmed

Acute therapy First-line treatment

Acute therapySecond-line treatment

Oxygen inhalation

Sumatriptan 6 mg s.c.

Zolmitriptan 5mg intranasally

Instillation of lidocain nasal spray (4 %)

Sumatriptan 20 mg intranasally

Zolmitriptan 5 mg p.o.

Important side effects

–

Sensation of tightness around the thoraxSensation of tightness around the thorax

–

Sensation of tightness around the thorax

Sensation of tightness around the thorax

Evidence of the therapeutic recommendation

↑↑ Effect proved in 2 RCTs (13, e38)

↑↑ Effect proved in 2 RCTs (e39, e40)

↑↑ Effect proved in 2 RCTs (e41, e42)*1

↑ Effect proved in 1 RCT (e15)

↑ Effect proved in 1 RCT (e43)

↑ Effect proved in 1 RCT (e44)*2


M E D I C I N E

serum concentrations in the therapeutic range, topira-mate >100 mg, indomethacin >150 mg to exclude par-oxysmal hemicranias or hemicrania continua, methy-sergide >8 mg, corticosteroids such as prednisolone >100 mg) (17).

Invasive and interventional therapeutic approaches in cluster headacheInvasive procedures do not represent an “alternative” treatment option to pharmacotherapy but an additional back-up option for treating severely impaired patients whose headaches are refractory to treatment.

Ablative procedures such as rhizotomy of the root exit zone of the trigeminal nerve or destructive procedures to the Gasserion ganglion have been aban-doned because of severe irreversible side effects (anesthesia dolorosa). Stereotactic radiosurgical inter-ventions (gamma knife) have proved effective in a small case series, albeit at the cost of persistent hypo-sensitization (e23).

Neuromodulation procedures provide a source of hope for patients with treatment-refractory cluster headaches in terms of reducing the number and severity of attacks.

Case reports and case series have been published on deep brain stimulation at the posterior hypothalamus at the transition to the upper tegmentum. Since the effect often sets in only after weeks or months, the mechan-ism of action is assumed to be due to complex neuro -plastic restructuring processes (18, e24). The initially published excellent response rates were reproduced at

slightly lower rates as the procedure became more widely available (average success rate about 50%) (18, 19, e25). A recent blinded study found no superiority of stimulation in the first month but a 50% reduction in at-tacks when stimulation was continued (e26). In one case, lethal hemorrhage occurred as a complication after deep brain stimulation, which reflects the poten-tial risks of stereotactic intervention independently of the indication (e27, e28).

Similarly good results were noted for stimulation of the occipital nerve. Modulation at the level of the spinal cord via convergence of afferences of the trigeminal nerve and the upper cervical marrow (C2/C3) in the trigemino-cervical complex is being discussed as a mechanism of action for bilateral chronic stimulation of the occipital nerve (e29–e31). The first successfully treated series of patients with chronic cluster headache reported a reduction in the intensity of pain and the fre-quency of attacks of 20% to 90%. Our own prospective studies have confirmed this; the effect can be expected to manifest after 4 to 6 weeks (20, 21). Because of the lower invasiveness of the procedure, we prefer bilateral stimulation of the occipital nerve to deep brain stimu-lation.

In spinal cord stimulation (SCS), an electrode is inserted epidurally high up in the cervical spine for the purpose of stimulation, but thus far only one case report has become available (e32); a scientific assessment of the procedure is currently not possible.

Therapeutic attempts have also been made using vagus nerve stimulation (VNS). A small case series

TABLE 3

Therapeutic recommendations for the prophylaxis of cluster attacks (modified from [12])

*1 Occasionally, dosages of up to 960 mg/day are required and tolerable*2 good c;inical efficacy from our point of view

↑↑ Recommendation supported by several adequate, valid, clinical studies (e.g. randomized controlled trials [RCTs]) or by one or several valid meta-analyses or systematic reviews. Positive result well confirmed.

↑ Recommendation supported by at least one adequate, valid, clinical study (e.g. randomized controlled trial). Positive result confirmed

ProphylaxisFirst-line treatment

ProphylaxisSecond-line treatment

Verapamil up to 560 mg*1

Corticoids (prednisolone, methylpredni -solone) 100 mg, higher dose if required

Lithium 600–1800 mg (targeted serum concentration by effectiveness: 0.4–1.2 mmoL/L)

Methysergide*2 8–12 mg

Topiramate 100–200 mg

Suboccipital injection of the occipital nerve with steroids and local anesthetics (occipital nerve block) *2

Important side effects

Cardiac conduction impairment (AV blockade), constipation, edema

Blood glucose imbalance, hypertension, sleep disturbance, aseptic bone necroses

Tremor, polyuria, polydypsia, thyroid dys-function, arrhythmias

Retroperitoneal fibrosis

Acral paraesthesias, difficulty speaking

Abscess, hair loss, procedural risks of injection

Evidence of the therapeutic recommendation

↑↑ Effect proved in 2 RCTs, important for treatment (e16, e17)

↑↑ Effect not proved in RCT, important for treatment despite lack of RCTs (10)

↑ Proved by open studies, no superiority in a controlled study vs placebo; use prima-rily in chronic cluster headache (e17, e45, e46)

↑↑ No RCT available (10)

↑ Proved by open studies, no RCT avail -able (e20, e47, e48)

↑ Effect proved in 1 RCT (15)


M E D I C I N E

showed an effect for migraine and cluster headache (e33, e34). However, so far the data do not permit any assessment of the short-term and medium-term effec-tiveness.

Stimulation of the sphenopalatine ganglion (SPG) is intended to enable treatment of attacks on the basis of ablative or local anesthetic effects (e35–e37). Initial re-sults using external stimulation units have been promising (22, 23). However, it remains to be seen whether this technology is also suitable for prophylac-tic treatment. These procedures should not be used out-side a clinical trial setting.

ConclusionsIn most patients it is possible by means of medication to satisfactorily treat and even prevent attacks of cluster headache, which is classed as the most severe headache disorder. Delays in reaching a diagnosis and therefore in administering treatment cause problems in this often underdiagnosed disorder. Neuromodulation therapies are available for patients with chronic cluster headache or for those whose headache is refractory to treatment, but their value is currently not clear. However, these treatment modalities give hope for improvements to the therapy of cluster headache, although they should be administered according to current guidelines in centers in the context of prospective studies (17).

Conflict of interest statementDr Gaul has received honoraria for participating in an advisory board from Desitin and Allergan. He has received honoraria in the context of a publication from Boehringer Ingelheim. He has received travel and hotel expenses and honoraria for speaking from Berlin Chemie, MSD, and Allergan. He has been reimbursed for conducting commissioned clinical studies from MSD, Novartis, Complen Health, CoLucid Pharmaceuticals, and Bial.

Dr Müller has received financial funding from St. Jude Medical and Medtronic for a patients’ information forum for cluster headache. He has also received travel and hotel expenses from both companies.

Professor Diener has received honoraria for planning, conducting, or partici-pating in clinical studies, participation in advisory boards or lectures from: Addex Pharma, Allergan, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers-Squibb, CoLucid, Coherex, GlaxoSmith-Kline, Grünenthal, Janssen-Cilag, Lilly, La Roche, 3M Medica, Menarini, Minster, MSD, Neurocore, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, SanofiAventis, St Jude Medical, and Weber & Weber. He has received financial funding for research projects from Allergan, Almirali, AstraZeneca, Bayer GSK, Janssen-Cilag, and Pfizer.

Manuscript received on 1 February 2011, revised version accepted on 4 April 2011.

Translated from the original German by Dr Birte Twisselmann.

REFERENCES

1. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004; 24 (Suppl 1): 9–160.

2. Evers S, Fischera M, May A, Berger K: Prevalence of cluster head-ache in Germany: results of the epidemiological DMKG study. J Neurol Neurosurg Psychiatry 2007; 78: 1289–90.

3. Schürks M, Kurth T, de Jesus J, Jonjic M, Rosskopf D, Diener HC: Cluster headache: clinical presentation, lifestyle features, and medi-cal treatment. Headache 2006; 46: 1246–54.

4. Bahra A, May A, Goadsby PJ: Cluster headache: a prospective clini-cal study with diagnostic implications. Neurology 2002; 58: 354–61.

5. Gaul C, Gantenbein AR, Buettner UW, Ettlin DA, Sándor PS: Orofa-cial cluster headache. Cephalalgia 2008; 28: 903–5.

6. Jürgens TP, Gaul C, Lindwurm A, et al.: Impairment in episodic and chronic cluster headache. Cephalalgia 2011; 31: 671–82.

7. May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ: Hypo -thalamic activation in cluster headache attacks. Lancet 1998; 352: 275–8.

8. May A: Cluster headache: pathogenesis, diagnosis, and manage-ment. Lancet 2005; 366: 843–55.

9. Obermann M, Yoon MS, Dommes P, et al.: Prevalence of trigeminal autonomic symptoms in migraine: a population-based study. Cephalalgia 2007; 27: 504–9.

10. May A, Leone M, Afra J, et al.: EFNS Task Force. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol 2006; 13: 1066–77.

11. Francis GJ, Becker WJ, Pringsheim TM: Acute and preventive phar-macologic treatment of cluster headache. Neurology 2010; 75: 463–73.

12. May A, Straube A, Limmroth V, et al.: Clusterkopfschmerz und trigeminoautonome Kopfschmerzen. In: Diener H, Putzki N, Berlit P, Deuschl G, Elger C, Gold R, et al. (eds.): Leitlinien für Diagnostik und Therapie in der Neurologie. 4th edition. Stuttgart: Thieme 2008; 576–2.

13. Cohen AS, Burns B, Goadsby PJ: High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA 2009; 302: 2451–7.

14. Law S, Derry S, Moore RA: Triptans for acute cluster headache. Cochrane Database Syst Rev 2010; (4): CD008042.

15. Ambrosini A, Vandenheede M, Rossi P, et al.: Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster head-ache: a double-blind placebo-controlled study. Pain 2005; 118: 92–6.

16. Goadsby PJ, Schoenen J, Ferrari MD, Silberstein SD, Dodick D: To-wards a definition of intractable headache for use in clinical practice and trials. Cephalalgia 2006; 26: 1168–70.

17. Jürgens T, Paulus W, Tronnier T, Gaul C, Lampl C, Gantenbein A, May A, Diener HC: Einsatz neuromodulierender Verfahren bei pri-mären Kopfschmerzen. Therapieempfehlungen der Deutschen Migräne- und Kopfschmerzgesellschaft. Nervenheilkunde 2011; 30: 47–58.

KEY MESSAGES

● Cluster headache is the most severe type of primary headache and is characterized by brief, one-sided attacks that are typically accompanied by trigemino -autonomic manifestations and restlessness.

● Successful treatment of the attacks with triptans (nasal or subcutaneous) or inhalation of pure oxygen has a sound scientific evidence base.

● High-dose verapamil (also suitable for long-term treat-ment) and a short course of corticosteroids are the ther-apies of choice for the prophylaxis of cluster headache. Lithium has become an established treatment modality for chronic cluster headache.

● Topiramate, ergotamine, melatonin, valproate, and me-thysergide represent further medication treatments; however, the evidence base is limited.

● Stimulation of the occipital nerve can be offered in centers to patients with chronic cluster headache that is refractory to treatment and is a less invasive approach to therapeutic neuromodulation than deep brain stimu-lation in the hypothalamic region.


M E D I C I N E

18. Rasche D, Klase D, Tronnier VM: Neuromodulation in cluster head-ache. Clinical follow-up after deep brain stimulation in the posterior hypothalamus for chronic cluster headache, case report—Part II. Schmerz 2008; 22 (Suppl1): 37–40.

19. Bartsch T, Pinsker MO, Rasche D, et al.: Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series. Cephalalgia 2008; 28: 285–95.

20. Mueller O, Gaul C, Katsarava Z, Sure U, Diener HC, Gasser T: Bilat-eral occipital nerve stimulation for the treatment of chronic cluster headache: case series and initiation of a prospective study. Fortschr Neurol Psychiartr 2010; 78: 709–14.

21. Mueller O, Gaul C, Katzarava Z, Sure U, Diener HC, Gasser T: Oc-cipital nerve stimulation for the treatment of chronic cluster head-ache – lessons learned from 18 months experience. Centr Europ Neurosurg 2011; 72: 84–9.

22. Tepper SJ, Rezai A, Narouze S, Steiner C, Mohajer P, Ansarinia M: Acute treatment of intractable migraine with sphenopalatine gan-glion electrical stimulation. Headache 2009; 49: 983–9.

23. Ansarinia M, Rezai A, Tepper SJ, et al.: Sphenopalatine ganglion (SPG) stimulation during acute migraine and cluster headaches. Cephalalgia 2009; 29 (Suppl.1): 28.

Corresponding author Dr. med. Charly Gaul Universitätsklinikum Essen, Neurologische Klinik Hufelandstr. 26 45147 Essen, Germany [email protected]

@ For eReferences please refer to: www.aerzteblatt-international.de/ref3311


dtsch_arztebl_int-108-0543

Documents